Scarlet fever antigen



Patented Mar. 15, 1927.

1 wmronn r.- LARSON, or mmnnaroms, mmnnsora.

SCARLET r'nvnn ANTIGEN.

No Drawing. Application filed .Tanuaiy 27, 1926, Serial No. 84,168. Renewed m It is the object of my invention to modify scarlet fever streptococci, (hemolytic streptococci,) their products and toxln, so that they may be used as antigens to immunize against scarlet fever, and may do so without requiring the relatively larger number of graduated injections required with the present type of scarlet fever toxin.

This application is in part a continuation of my co-pendingsapplication Serial No. 52,963, filed August 27, 1925.

Scarlet fever toxin has been produced from the scarlet been used as an antigen to immunize agalnst scarlet fever, Moreover, the scarlet fever streptococci themselves have been used as antigens to cause the production of anti body serum; and this has been done both with living and dead streptococci.

However, prior to my invention, in producing immunization with the unmodified scarlet fever streptococci, living or dead, and/or their products or toxins, it has been necessary to give a seriesof injections, ordinarily ranging from 3 to 10, of successively increasin size; the first dose being 7 ally created.

- treating the streptococci,

sufficient size so that ordinarily fairly small, and succeeding doses beinglarger as immunity is gradu- This requires a rather long period of time, and considerable inconvenience.

By modifying the scarlet fever. strepto' cocci, their products or toxins, in accordance with my invention, I am able to give a patient a relatively large injection of immunity may ordinarily be obtained from-a single injection? I have discovered that the scarlet fever streptococci, or their products or toxin, or both, may be attenuated to lower very greatly the peak toxicity thereof, probably with alonger duration of the toxic action and a wider area of action in the body, by their products or toxins, or both, with a suitable agent which produces such reduction in peak toxicity while leaving the material antigenic. I have discovered that this is the case whether the streptococci: are living organisms, or are dead organisms; and that it may be done on the toxin alone, on the organisms alone, whether livin or dead, or on the mixture of the living or cad organisms with the toxins thereof. The treatment of the scarlet fever organisms their products or toxins, sirably sufficient to reduce. the peak toxicity fever streptococci, and has soap may of a mixture of the streptococci scarlet fever streptococci, their is deember 26, 1926.

to a point Where a dose as large as a plurality of normal first immunizing doses may be injected without greater discomfort or greater ill effects than such a normal first dose has; while maintaining such treated,

material sufliciently antigenic to incite the production of immunity against scarlet fever in the inoculated person.

The scarlet fever streptococci, or their products or toxins, or both, are attenuated or detoxified by treating them with a soluble salt of one of the higher fatty acids, which salts are commonly designated as soaps and are all surface-tension depressants, (or capillary active substances, the two terms be,- ing synonymous) or with a soluble salt of some other organic acid which is 'a sur face-tension depressant. The salts to employ are derived from fatty acids having melting points below 44 C. and are soluble in water at that or a lower temperature. Of'these, I prefer the salts derived from unsaturated fatty those having one or more hydroxyl such as a soluble salt of especially purified castor to work with the castor oil soap solution at pH of 7.4 to 8.0, withinwhich pHrange the desired attenuating effect is. at a maximum. The treatment with the castor oil be of the living scarlet fever streptococci, or of the dead scarlet fever strep 'tococci, (killed in any manner, as byheat or by a bactericide,) or of the products or toxin. obtained from such str tococci, or (living or' produced oups, r1c1nole1c acid, and

dead) and the products or toxins thereby. I prefer to useeither they toxin itself, free from the organisms, as the basis for the treatment; or else to use a vaccine consisting of dead streptococci mixed with,

the toxin produced thereby While they were living; as the basis for the treatment with the castoroil soap. 7

The concentration of the castor oil soap solution after mixture therewith of the toxins, may vary considerably. In .my experience, this concentration should' be 'between 0.1% and 20%, and is desirably-about 1% to 2%, after such mixture. 7 the soap solution is in .such mixture, the larger the volume oftii'e soap solution should be for a given quantity of the streptococci,

acids, particularly oil soap. I prefer products or The weaker their products'or toxins; aiid, conversely,

the smaller the volume of soap solution used,

i the greatershould be its concentration. I prefer to use the soap solution in such concentration that the volume to be injected of the mixture of the soap with the streptococci or their products or toxin, or wit both, should not exceed 2 c. 0.; but this is merely for convenience in injection.

The. mixture is allowed to stand at least a suflicient time .to permit it to reach equilibrium before it is injected; which time varies with the concentration of the soap solution, in inverse sense to such concentration. The surface-tension depressant, such as thecastor oil soap, renders the scarlet fever streptococci, their products or toxins, sufliciently non-poisonous so that the dose may be .increased many fold; yet the streptococci, their products or toxins, retain their stimulatin power as an antigen, so that they incite in e inoculated person the production of. scarlet fever anti-toxin or anti-bacterial bodies, which serve to immunize against the disease. A

The action on the modified streptococci, their'products or toxins, in the human body, is due to an adsorption action, probably of the fattysacid'asalt on the bacterial organisms or on the toxin molecules, or on both, so that upon injection theantigen is at first partially or entirely restrained from exerting its "poisonous action, which would otherwise cause a serious reaction, or even death tive if the dose were of suflicient size. My exerience indicates .that' following the in- ]ection the anti en is slowly released from this adsorbed atty-acid salt, so that the antigen has its effect spread out over a relay longerperiod of time instead of being suddenly effective, continued stimulation on the body of the inoculated person causes a buildin up of resistance by rapidly and continuous y creating the corresponding anti-bodies througher-continued period of stimuout such long lation'followmg the injection of the modl- 'fied bacterial organisms and/or modified toxin.

- with it into the bod unit of area ate production of anti-bod' agreater and more rapi which is ordinarily My experience also furnishes evidence that the fatty-acid salt, perhaps by its capacity promotes penetration of the antior bacterial organisms) mixed tissues so th distributed through to dialyze,

toxin anti en is more wide the T) y stimulatory action 'over a wider area; with a maintenance of the stimulating effect er below a critical maximum beyond which ill efiects and a less proportionoccur, and with' .total production of anti-bodies because of the increase in area of the stimulation. a with the use of my modified scarlet. fever antigen, 1 may give as the first injectionthe only injection recomfort than the ordinary smaller size living or and the resultant longertheir roducts or 'toxins, -an

. their (products or toxins, and

ody and thus exerts its antigenic or 111g one or more a of recmoleic acid.

(paired-a dose which is from 25 to 100 fold t e normal first dose of unmodified antigen. This injection may. be made in the usual manner, ordinarily subcutaneously, or intramuscularly if desired. This greatly increased dose is foundzto roduce less first dose of much of the unmodified toxin; and a single dose of my modified antigen of the size indicated above usually produces scarlet fever immunit If desired, -the antigen and the fatt acid salts may be dispensed in separate via s, of suitably proportioned size; so that the physician may himself mix the contents of the two vials a suitable time prior to injection.

In the following claims, of the components of the mixture, I use the expression scarlet fever streptococci, and/or their products or toxins, to denote'either the scarlet fever streptococci alone, whether in defining one saidscarlet fever streptococci, or a of such scarlet fever streptococc alone of amixture (living or produced thereby. I

I claim as my invention:

1. A composition of'matter, comprising a mixture of scarlet fever streptococci, and/or their products or toxins, and a soluble salt of an organic. acid which is a surface-tension depressant. f

2. A composition of matter, comprising a 1 mixture of scarlet fever streptococc1,and/or their roducts or toxins, and a surface-tension epressant comprising a soluble salt of a higher fatty acid.

3. A'composition ofmatter, comprising a mixture of scarlet fever stre tococcl and/or a sur aoe-ten-' e ressant comprising a acid.

sion of a. big er unsaturated fatty 4. A composition of matter, comprising a mixture of scarlet fever streptococci and/or, sion epressant a'soluble salt of. a-higher fatty ac'd containing one or more hydroxyl groups:

5. A compos comprisin ition-of matter, comprising a mixture of scarlet fever streptococci and/or their products'or toxinsfland a sur ace-tension dephressant comprising a soluble salt fatty acid contain er unsaturated hydroxyl groups. 6. A composition of matter, comprising a mixture of scarlet fever. streptococc1,and/or-' their roducts or toxins, and a soluble salt of ahig A composition of matter, comprising a mixture of scarlet feyer stre tococc1, and/or their products or toxins, an castoroil soap.

In witness whereof, I have hereunto set my hand this 25th da8 of January, 1926.

WIN}? RD P. LAB N.

dis-

dead, or' the products or toxins a0 5 dead) and the products or toxins soluble salt a. sur ace-ten- P lie I 

